Exploiting Interfacial Design for the Electrocatalytic Construction of C-C bonds

利用界面设计电催化构建 C-C 键

• 批准号: 10713693
• 负责人: Anna Wuttig
• 金额: $ 34.41万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713693
• 关键词: Adopted; Adoption; Alcohols; Aldehydes; Chemicals; Complex; Coupling; Disease; Electricity; Electrodes; Elements; Generations; Ketones; Medicine; Methods; Pharmacologic Substance; Preparation; Property; Reaction; Research; Solid; design; drug development; drug discovery; forging; functional group; improved; interfacial; prevent; programs

PROJECT ABSTRACT The objective of our research is to access new chemical spaces in drug discovery and development by reimagining the catalytic conditions for electricity-driven organic transformations. We propose a synthetic platform to couple every major class of C(sp3) organic halide electrophile with aldehyde and ketones. By fine- tuning the key electrophile interactions with the electrode material by interfacial design, we propose to forge C(sp3)–C(sp3) bonds with high selectivity and stereoselectivity. Our approach will provide direct and catalytic access to new chiral alcohol and α,α-difluorobenzylic derivatives, prevalent motifs in several high-profile pharmaceuticals, from accessible feedstocks. Our synthetic methods will provide complementary and direct approaches to access (enantio)selective C(sp3)–C(sp3) bonds that are restricted to non-catalytic or multi-step reactions. Non-catalytic reactions require either the generation of highly reactive reaction intermediates that degrade bioactive functional groups or the use of expensive and rare elements that limit wide-spread adoption. In addition to increasing the accessibility to prepare and diversify pharmaceuticals via electrocatalytic C(sp3)– C(sp3) bond formation, our mechanistic and structural analyses of electrified interfaces will dissect the fundamental properties that control interfacial reactivity in complex electrosynthetic manifolds. Thus, our program will reveal how new mechanisms to construct C(sp3)–C(sp3) can be accessed by engaging a recoverable and infinitely reusable solid electrocatalyst interface; an inherently sustainable synthetic approach that can be readily adoptable by medicinal chemists.

项目摘要 我们的研究目标是通过以下方式进入药物发现和开发中的新化学空间 重新设想电力驱动的有机转化的催化条件。我们提出了一种合成的 每个主要的C(SP3)有机卤化物亲电试剂与醛和酮偶联的平台。通过罚款- 通过界面设计调整关键的亲电相互作用与电极材料，我们建议锻造 C(SP3)-C(SP3)键具有高选择性和立体选择性。我们的方法将提供直接和催化 获得新的手性醇和α，α-二氟苯基衍生物，几个备受瞩目的流行基序 制药，从可获得的原料中提取。我们的合成方法将提供互补和直接的 限制为非催化或多步反应的(对映体)选择性C(SP3)-C(SP3)键的方法 反应。非催化反应需要生成高活性的反应中间体， 降解生物活性官能团或使用限制广泛采用的昂贵和稀有元素。 除了通过电催化C(SP3)增加制备药物和使药物多样化的可及性之外- C(SP3)键的形成，我们对带电界面的机理和结构分析将剖析 复杂电合成流形中控制界面反应性的基本性质。因此，我们的节目 将揭示如何通过使用可恢复的和 无限可重复使用的固体电催化剂界面；一种固有的可持续的合成方法，可以很容易地 可供药用化学家采用。